This project is concerned with the analysis, synthesis, and structure- function relationships of biologically active peptides. During this project year, (1) the design and synthesis of peptide antigens for immunological studies of the structure-function relationships of receptor molecules, (2) peptide conformation and peptide-membrane interactions in relation to biological activity or a modified activity spectrum are the focus. Three segments from different domains of a recently cloned angiotensin II receptor sub-type were selected, synthesized and conjugated to thyroglobulin. Different strategies were employed in order to achieve homogeneous linkage only at one point of the peptide in an attempt to maximize the specificity of the generated antibodies. Three segments, The N-terminal peptide, res. 1-26, the C- terminal portion, res. 325-359 and a putative glycopeptide segment, res. 180-192 and their thyroglobulin conjugates were prepared. Generation of antisera against these peptides is in progress. The antisera when available will have great utility for the study of angiotensin II receptor tissue distributions, expression and inhibition of AII associated signal transduction. Synthetic magainins A (MA) and G (MG) are highly potent against bacteria and protozoa. These two peptides were also tested against six small cell lung cancer cells (SCLC). The average IC50 of MA and MG were almost equally potent (8.64 vs. 8.82 micros) where the most effective chemotherapeutic agent, cisplatin yielded IC50=2.6 micros. Despite a 10- fold difference in sensitivity among different SCLC to standard chemotherapeutic agents, the IC50 of MA or MG differs by less than 3- fold. The toxicity of MA or MG against fibroblast cell lines was insignificant. Approximately 50-100% synergistic effects were observed when MA or MG were used in conjunction with cisplatin or etoposid. An interaction of two helical chains can be characterized by measuring a ratio of ellipticities at 222 ([theta]222) and 208 ([theta]208) on CD spectra. Although MB generally shows no secondary structure in aqueous solution, it not only displays a spectrum indicative of alpha-helix but also yields a ratio ([theta]222/[theta]208) of greater than one of the peptide concentration exceeds 300 micros. This led us to investigate the CD spectra of dimeric MB analogues cross-linked with added cystine at either N- or C-terminus. Both dimeric analogues displays a ratio greater than 1 at 0.5 micros level. The N-dimer promotes helical formation more effectively and the helices are more stable than those of C-dimer. These results further support the ability of MB to form helical coiled-coil structure. This structure may be induced by the hydrophobic zipper-type interactions between the phenyl rings of Phe residues at positions 5, 12, and 16.